An extremely challenging orthopedic task has been the architectural reconstruction of osseous defects which may have been a sequela of infection induced bony sequestration, developmental malformation, surgical resection, or traumatic avulsion. The need to initiate repair and to restore structurally deficient bone has inspired the development and application of a bewildering array of materials.
Autogeneic and allogeneic agents have been employed for orthopedic and maxillofacial skeletal procedures. However, an overall failure rate of 13-30% for autografts and even greater failure rate for allografts and alloimplants militate against unequivocal, universal acceptance of these materials for bone repair and replacement. Preparation of xenogeneic substances by current methods for human application is considered to be unacceptable. See for example, Urist, M. R., Fundamental and Clinical Bone Physiology, pp. 331-368, (1981).
Bone derivatives (i.e., demineralized bone), collagen gels, and ceramics of various stoichiometries have been investigated for osseous repair and augmentation. Antigenicity and the diversity and unpredictability of the host rsponses to these agents have precluded immediate clinical application.
Investigators have used biodegradable bone plates and screws prepared from the homopolymer polylactic acid (PLA) to repair and stabilize mandibular and orbital features. After 32-36 weeks these devices were still detectable microscopically, and although biocompatibility, osseous healing, and osteoconduction were evident at the repair sites, the slow biodegradation of the PLA may be considered a deterrent to bone healing. Applicant fabricated a copolymer of polylactic acid (PLA) and polyglycolic acid (PGA) that had significantly different chemical and physical properties from the PLA homopolymer. Experimental evidence suggested that the copolymer formulation might be osteoconductive and osteoinductive.
A basic protein-acidic phospholipid complex that has been isolated from Bacterionema matruchotii has been shown to induce hydroxyapatite formation in vitro. A similar proteolipid consisting of mucopeptide-N-acetyl-muramoylhydrolase and phosphatidyl inositol 4,5-diphosphate has been tested in vivo and evaluated histomorphometrically by applicant. It was determined that the rate of bone formation was more rapid at sites treated with this agent than at non-treated control sites.
The proteolipid in the form investigated by applicant has a paste-like consistancy. This physical attribute is usually not satisfactory for repairing many types of osseous defects. Preliminary studies revealed that when the PLA:PGA copolymer is in a doughy state it may be combined with the proteolipid. After curing, a rigid, porous, and bone-like material can be produced that can be carved into any desired shape.
Applicant has discovered that a copolymer of PLA:PGA combined with a proteolipid will facilitate improved healing of osseous wounds. The evaluation of applicant's findings was accomplished by quantitating elements of bone repair (i.e., cellular, osteoid, trabeculae) using computer assisted histomorphometric analysis of selectively stained specimens obtained from osseous wounds treated with the copolymer-proteolipid material.
The ultimate objective of applicant's investigation was to promote the development of a bone repair and replacement compound that will be immunologically acceptable; nontoxic; commensurate in physical properties to bone; osteoconductive; osteoinductive; replacable at controlled and predictable rates by osseous tissue; readily available; easily and conveniently shaped; suitable for rigid fixation; and esthetically and functionally capable of integrating with existing anatomical structures.